Technique for adjusting the locus of excitation of electrically excitable tissue

ABSTRACT

The locus of electrically excitable tissue where action potentials are induced can be controlled using the physiological principle of electrotonus. In one embodiment, first and second pulses are applied to first and second electrodes, respectively, to generate first and second subthreshold potential areas, respectively, within the tissue. The locus within the tissue where action potentials are induced is determined by a superposition of the first and second subthreshold areas according to the physiological principle of electrotonus. In another embodiment, a two-dimensional array of electrodes are formed. The cathode may be positioned near the center of the two-dimensional array or may be left out. The first and second subthreshold areas may thereby be steered. An array of anodal rings may be used to contain the field of excitation.

BACKGROUND OF THE INVENTION.

This is a continuation-in-part of the earlier filed co-pending patentapplication Ser. No. 09/312,470 filed on May 17, 1999, now U.S. Pat. No.6,083,252 which is a divisional of patent application Ser. No.08/814,432 filed on Mar. 10, 1997, now U.S. Pat. No. 5,925,070, which isa continuation-in-part of patent application Ser. No. 08/637,361 filedon Apr. 25, 1996, now U.S. Pat. No. 5,713,922, which is acontinuation-in-part of patent application Ser. No. 08/627,578 filed onApr. 4, 1996, now abandoned, for which priority is claimed. Thesepatents and patent applications are each incorporated herewith byreference in their entireties.

FIELD OF THE INVENTION

This invention relates to means of stimulating electrically excitabletissue, and more particularly relates to means for adjusting the locusat which action potentials are induced in such tissue.

DESCRIPTION OF THE RELATED ART

Two major practical problems reduce the efficacy of epidural spinal cordstimulation (SCS) for pain control. One is the difficulty of directingthe stimulation-induced paresthesia to the desired body part and theother is the problem of disagreeable sensations or motor responses tothe stimulation, which reduce the comfortable amplitude range of thestimulation. It is generally agreed that in SCS, for chronic pain,paresthesia should cover the whole pain region. With present stimulationmethods and equipment, only highly skilled and experienced practitionersare able to position a stimulation lead in such a way that the desiredoverlap is reached and desired results are obtained over time withminimal side effects. It requires much time and effort to focus thestimulation on the desired body region during surgery and, using pulseswith single value cathodes, it is difficult to redirect it afterwards,even though some readjustments can be made by selecting a differentcontact combination, pulse rate, pulse width or voltage.

Redirecting paresthesia after surgery is highly desirable. Even ifparesthesia covers the pain area perfectly during surgery, the requiredparesthesia pattern often changes later due to lead migration, orhistological changes (such as the growth of connective tissue around thestimulation electrode) or disease progression. The problem of leadplacement has been addressed by U.S. Pat. No. 5,121,754 by the use of alead with a deformable distal shape. These problems are not only foundwith SCS, but also with peripheral nerve stimulation (PNS), depth brainstimulation (DBS), cortical-stimulation and also muscle or cardiacstimulation;

The era of precise control of electrical fields for excitation of tissueby use of multiple voltages is disclosed in PCT InternationalPublication No. WO 95/19804 (counterpart to Holsheimer et al., U.S. Pat.No. 5,501,703) (the “Holsheimer references”). The Holsheimer referencesdescribe the use of electrodes that are “in-line,” namely that they aredisposed “symmetrically” along a line. The three juxtaposed electrodeshave two simultaneous voltages relative to one of them, each with itsown amplitude. This approach allows “steering” of the electric fieldscreated by these electrodes. Particularly, the electrical field patternis adjusted by varying the electrical field generated between thoseelectrodes along that line. The locus of excitation is correspondinglyvaried with that variation in the electrical field pattern. For example,if a central electrode of three roughly collinear electrodes is acathode (−) then the outer anodes push the areas of excitation towardthe middle, and shield outer areas from excitation. As the anodal pulsesare varied in amplitude, the field steers toward the outside.

However, the Holsheimer references disclose a system that requires threeelectrodes that are optimally spaced symmetrically along a line. It is aserious handicap during the surgical procedure to place these electrodesin the body. Qften, a lead such as a paddle is used for mounting themultiple electrodes in the optimally spaced positions. This lead is theninserted within a patient near the tissue to be excited, and electricalexcitation is applied to the lead. Unfortunately, placement of a leadsuch as the paddle within a patient, can be difficult since the paddlecan be surgically difficult to manipulate adjacent the spinal cord.Thus, it would be desirable to be able to adjust the locus of excitationin electrically excitable tissue without the use of optimally spacedelectrodes.

In addition, the Holsheimer system is limited in that steering isaccomplished over a linear path. It would be desirable to adjust thelocus of excitation in electrically excitable tissue over a greaterarea.

OBJECTS OF THE INVENTION

Accordingly, a primary object of the present invention is to provide amethod and apparatus for adjusting the locus of excitation inelectrically excitable tissue using electrodes that do not have to beoptimally spaced in a line.

In particular, an object of the present invention is to adjust areas ofsubthreshold excitation in order to adjust an area of superposition ofsuch areas of subthreshold excitation. The area of superpositiondetermines the locus of excitation of electrically excitable tissue.

Another object of the invention is to provide a method and apparatus foradjusting the locus of super threshold excitation in electricallyexcitable tissue using electrodes that are spaced in a two dimensionalarray.

Another object of the invention is to add outer anodes to a grouping ofcathodal electrodes to shield areas farther out and to keep activationof tissue nearer to the cathodes.

SUMMARY OF THE INVENTION

In a principle aspect, the present invention takes the form of anapparatus and method for inducing action potentials at an adjustablelocus of electrically excitable tissue. In accordance with theinvention, a first pulse having a first amplitude and a first pulsewidth is applied to the tissue via. a first electrode adapted to beadjacent said tissue. Similarly, a second pulse having a secondamplitude and a second pulse width is applied to the tissue via a secondelectrode adapted to be adjacent said tissue.

The application of the first pulse generates a first subthresholdpotential area in said tissue, and the application of the second pulsegenerates a second subthreshold potential area. The first subthresholdarea is determined by the first amplitude and the first pulse width ofthe first pulse, and the second subthreshold area is determined by thesecond amplitude and the second pulse width of the second pulse. Asuperposition of the first and second subthreshold areas results in asuprathreshold potential area of said adjustable locus where the actionpotentials are induced.

This embodiment of the present invention may be applied to particularadvantage when adjusting the locus where the action potentials areinduced. The first amplitude or the first pulse width of the first pulsecan be adjusted for a corresponding adjustment of the first subthresholdarea and contribute, in turn, to the volume where suprathresholdpotentials are produced. Similarly, the second amplitude or the secondpulse width of the second pulse can be adjusted for a correspondingadjustment of the second subthreshold area and contribute, in turn, tothe volume of where suprathreshold potentials are produced. The size andlocation of the suprathreshold potential area can thus be controlled.

In another aspect of the present invention, a time delay between theapplication of the first and second pulses can be varied for acorresponding adjustment in size and location of the suprathresholdpotential area. The time delay between the application of the first andsecond pulses can be measured from the end time of the first pulse tothe begin time of the second pulse. Additionally, that delay can bemeasured as a difference between a first weighted average time of thefirst pulse and a second weighted average time of the second pulse, orbetween a first peak time of the first pulse and a second peak time ofthe second pulse.

In another aspect of the invention, simultaneous pulses of varyingamplitudes are delivered to multiple electrodes (cathodes), which arearranged in a two-dimensional array. As a cross-pattern, there may be acentral electrode at the center of the pattern, which is the mostcathodal (negative). By having the outer four electrodes to be lesscathodal (not as negative), or even fully positive (anodal), the locusof cells that have suprathreshold activation can be shifted in twodimensions. With such constraining of the fields, the amplitude can beincreased, driving the locus of activation deeper into the tissue,thereby creating a third dimensional effect.

In yet another aspect of the invention, the two-dimensional array ofcathodes may be surrounded by an outer ring of anodes to keep the locusof activation contained and to shield outside tissue from activation.

In still another aspect of the invention, a combination of simultaneousand delayed cathodal pulses are applied on some electrodes in an array.Each pulse creates an area of subthreshold excitation, and thecombination provides a controlled locus to the threshold for theproduction of action potentials.

These and other features and advantages of the present invention will bebetter understood by considering the following detailed description ofthe invention which is presented with the attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other advantages and features of the invention will becomeapparent upon reading the following detailed description and referringto the accompanying drawings in which like numbers refer to like partsthroughout and in which:

FIG. 1 is a diagramunatic view of a patient in which a preferred form ofapparatus for SCS made in accordance with the invention has beenimplanted;

FIG. 2 is a cross-sectional view of an exemplary spinal column showing atypical position at which electrodes made in accordance with thepreferred practice of the invention have been implanted in the epiduralspace;

FIG. 3 is a cross-sectional view like FIG. 2 showing locus of potentialchanges induced in cells of the spinal cord from a pulse applied to afirst one of two electrodes;

FIG. 4 is a view like FIG. 3 showing the locus of potential changesinduced in cells of the spinal cord from the application of a pulse tothe second of the electrodes;

FIG. 5 is a view like FIG. 4 showing the combined loci in the spinalcord at which potential changes are induced from pulses applied to thefirst and second electrodes;

FIG. 6 is a view like FIG. 5 showing the alteration of the loci due toincrease in the amplitude of the pulse applied to the first electrodeand a decrease in amplitude of the pulse applied to the secondelectrode;

FIG. 7 is a view like FIG. 6 showing the alteration of the loci due toan increase in amplitude of the pulse applied to the second electrodeand a decrease in amplitude of the pulse applied to the first electrode;

FIG. 8 is a timing diagram showing pulses applied to the first andsecond electrodes illustrated in FIG. 2 in relationship to the potentialchanges induced in tissue adjacent the electrodes;

FIGS. 9 and 10 are timing diagrams illustrating alternative forms ofpulses applied to the electrodes illustrated in FIG. 2; and

FIG. 11 is a timing diagram illustrating a preferred form of pulsesapplied to the electrodes shown in FIG. 2.

FIG. 12 shows the suprathreshold potential area generated fromapplication of two pulses to two electrodes where the two pulses havinga first time delay between the end of the first pulse and the start ofthe second pulse.

FIG. 13 shows the suprathreshold potential area generated fromapplication of two pulses to two electrodes where the two pulses have asecond time delay between the end of the first pulse and the start ofthe second pulse, with the second time delay being greater than thefirst time delay of FIG. 12.

FIG. 14 shows the suprathreshold potential area generated fromapplication of two pulses to two electrodes where the two pulses have athird time delay between the end of the first pulse and the start of thesecond pulse, with the third time delay being greater than the secondtime delay of FIG. 13.

FIG. 15 shows the suprathreshold potential area generated fromapplication of two pulses to two electrodes where the two pulses have afourth time delay between the end of the first pulse and the start ofthe second pulse, with the fourth time delay being greater than thethird time delay of FIG. 14; and

FIGS. 16-25 depict various arrays of electrodes that may be used inaccordance with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIG. 8, a single electrical pulse P1 can causedepolarization near a cathode in electrically excitable tissue whichincludes neural tissue or muscle tissue. Neural tissue includesperipheral nerves, ganglia, the spinal cord surface, deep spinal cordtissue, deep brain tissue, and brain surface tissue. Muscle tissueincludes skeletal (red) muscle, smooth (white) muscle, and cardiacmuscle. A locus includes a set of points in three-dimensional space andrefers to a volume of cells or parts of cells. Due to the electricalcharacteristics of both the three-dimensional volume conductor and themembrane properties, the potentials outside and inside a neuron respondto the depolarization, usually with inverse exponential-type increasesduring the pulse and then attenuation over time after the pulse. Thetime constant for an isolated neuron membrane typically is 5-15milliseconds (Nerve, Muscle and Synapse by Bernard Katz, circa 1972).For myelinated axons or muscle cells, it may be considerably shorter.

A living cell at any time has a transmembrane potential across itsmembrane. This transmembrane potential is typically defined as thepotential in the inside of the cell with respect to the outside of thecell. At rest, a living cell has a constant transmembrane potentialcalled a resting potential of approximately −60 mV to −90 mV, with theinside of the cell being more negative than outside of the cell. Avariety of changes to the environment of the living cell can result in acorresponding change in the transmembrane potential.

A change in the environment that causes the inside of the cell to becomeless negative is referred to as a “depolarization” of the cell, anddepolarization is then a positive change in the transmembrane potential.Similarly, a change in the environment that causes the inside of thecell to become more negative is referred to as a “hyperpolarization” ofthe cell, and hyperpolarization is a negative change in thetransmembrane potential. An example of change in the environment of aliving cell is when a voltage pulse is applied near the cell. Dependingon the direction of the electric current caused by this stimulationpulse, the pulse can be either depolarizing or hyperpolarizing.

FIG. 8 shows an example pulse P1 that can cause time varyingdepolarization in a cell, and this depolarization from application ofpulse P1 adjacent the cell can result in changes in a transmembranepotential TPA1. A further application of another pulse P2 adjacent thecell results in a portion of the curve TPA2. TPA3 is a superposition ofthe depolarizations caused by both pulses P1 and P2. The remainingdepolarization from the prior application of pulse P1 between times T3and T7 is shown by the dashed line curve in TPA3.

The transmembrane potential TPA1 is comprised of two components. Thefirst component is the resting potential of the cell. This component isa constant gradient that exists across the membrane of the cell due tosteady state ionic concentrations. Added to that first component is thedepolarization that results from the application of pulse P1. Thus,transmembrane potential TPA1 is the sum total of the resting potentialwith the depolarization effects from application of pulse P1.

The sum total transmembrane potential TPA1 or TPA2 at any time mustreach a certain transmembrane potential threshold TPT in order for theelectrically excitable cell to get an action potential induced therein.The peak of potential TPA1 or TPA2 is below the transmembrane potentialthreshold TPT, and thus potential TPA1 or TPA2 can be characterized as asubthreshold potential. As a result, the potential changes from pulsesP1 or P2 alone fail to produce an action potential in that cell. Evenwhen pulses P1 and P2 occur with a time delay (T3-T2), the tansmembranepotential TPA3 may still not reach the transmembrane potential TPT.

Action potential is an all-or-none, nonlinear phenomenon, caused byopening of sodium gates, inrush of sodium ions, and a delayed opening ofpotassium gates and a restoration of the membrane potential. In general,a certain amount of charge must be passed at the electrodes (amplitude[Volts] /resistance [Ohms] x pulse width [time]) in order to causeenough depolarization for an action potential to begin. There is areciprocal relationship between amplitude and pulse width: the productmust reach a certain value before the transmembrane potential thresholdis reached. This relationship does not reach the Volts=0 axis. There isa certain minimum voltage needed, called rheobase, before an actionpotential can happen.

Basic neurophysiological principles, called “electrotonus”, show that inany volume of electrically excitable tissue, if two or more depolarizingpulses tending to induce action potentials, each of which alone isinsufficient to bring the cells to threshold, arrive closely together intime, at least part of their effect is additive, i.e., the memory of thefirst pulse is still present when the second pulse arrives. If the sumof the potentials (distorted by resistive and capacitive properties ofthe surroundings and the cell membranes) can get some cells depolarizedto threshold, then an action potential will start in those cells. Areference that explains these principles of “electrotonus” including thecreation of subthreshold potentials is Medical Physiology, 13th Edition,Vol. 1, by Vernon B. Mountcastle, C. V. Mosby Co., 1974.

Still referring to FIG. 8, the inducement of an action potential in acell is illustrated by a transmembrane potential TPB reaching thetransmembrane potential threshold TPT at time T4. TPB can becharacterized as a suprathreshold potential, and the nerve tissue has anaction potential started when TPB reaches the transmembrane potentialthreshold (at time T4). The transmembrane potential TPB is comprised ofthe constant resting potential and a depolarization that is sufficientenough to push the total transmembrane potential TPB above thetransmembrane potential threshold. TPB at time T4 has sufficientdepolarization to go above the transmembrane potential threshold becausethe amplitude of pulse P2 may have either been larger than in the caseof the subthreshold transmembrane potential TPA2 or have come soonenough before the memory of the effect of pulse P1 has subsided.

FIG. 1 is a schematic view of a patient 10 having an implant of aneurological stimulation system employing a preferred form of thepresent invention to stimulate spinal cord 12 of the patient. Thepreferred system employs an implantable pulse generator 14 to produce anumber of independent stimulation pulses which are sent to spinal cord12 by insulated leads 16 and 18 coupled to the spinal cord by electrodes16A and 18A (FIG. 2). Electrodes 16A and 18A. also can be attached toseparate conductors included within a single lead.

Implantable pulse generator 14 preferably is a modified ITREL IIimplantable pulse generator available from Medtronic, Inc. withprovisions for multiple pulses occurring either simultaneously or withone pulse shifted in time with respect to the other, and havingindependently varying amplitudes and pulse widths. This preferred systememploys a programmer 20 which is coupled via a conductor 22 to a radiofrequency antenna 24. This system permits attending medical personnel toselect the various pulse output options after implant using radiofrequency communications. While the preferred system employs fullyimplanted elements, systems employing partially implanted generators andradio-frequency coupling may also be used in the practice of the presentinvention (e.g., similar to products sold by Medtronic, Inc. under thetrademarks X-trel and Mattrix).

FIG. 2 is a cross-sectional view of spine 12 showing implantation of thedistal end of insulated leads 16 and 18 which terminate in electrodes16A and 18A within epidural space 26. The electrodes may be conventionalpercutaneous electrodes, such as PISCES(® model 3487A sold by Medtronic,Inc. Also shown is the subdural space 28 filled with cerebrospinal fluid(cfs), bony vertebral body 30, vertebral arch 31, and dura mater 32. Thespine also includes gray matter 34 and dorsal horns 36 and 37 and whitematter, for example, dorsal columns 46 and dorsal lateral columns 47.

Stimulation pulses are applied to electrodes 16A and 18A (whichtypically are cathodes) with respect to a return electrode (whichtypically is an anode) to induce a desired area of excitation in thespine 12 having nerve tissue capable of producing action potentials. (Acathode has a more negative potential with respect to an anode, and theelectrical current caused by the cathode tends to induce an actionpotential whereas the electrical current caused by the anode tends toinhibit an action potential.) The return electrode, for example a groundor other reference electrode, is also present but is not shown in thecross sectional view of spine 12 because the return electrode is locatedtypically at a different plane from the shown cross section of FIG. 2.For example, the return electrode may be located near a point up or downthe line along the spinal column 12 or at a more remote part of the body10 carrying the spine, such as at the metallic case of the pulsegenerator 14. Alternatively, more than one return electrode may bepresent in the body. There can be a respective return electrode for eachcathode such that a distinct cathode/anode pair is formed for eachcathode.

Referring to FIG. 8, pulse P1 is applied to electrode 18A (FIG. 2) andpulse P2 is applied to electrode 16A (FIG. 2). Pulses P1 and P2 have atiming relationship. For optimal operation of the present invention withthe application of the principle of “electrotonus”, pulses P1 and P2should not overlap in time. For example, the end of pulse P1 at time T2and the start of pulse P2 at time T3 in FIG. 8 are displaced by apredetermined time period less than 500-2000 microseconds, andpreferably less than 50-500 microseconds. Amplitude A1 of P1 isadjustable independently from amplitude A2 of pulse P2. The pulse widthsof pulses P1 and P2 also are independently adjustable. Widening thepulse widths of each pulse (i.e., P1 and P2) can also expand the loci ofdepolarizations, just like increasing amplitude, either voltage orcurrent amplitude.

The pulses P1 and P2 also could have other time delay relationships inorder to accomplish the goals of the present invention. Referring toFIG. 9, pulses P3 and P4, having different rise times, could be used. P3has a rise time from T1 to T8 and P4 has a rise time from T1 to T9.Referring to FIG. 10, pulses P5 and P6, having different fall times,could be used. P5 has a fall time from T10 to T11, and P6 has a falltime from T10 to T12. The weighted average time WA3 of pulse P3 (FIG. 9)is displaced from the weighted average time WA4 of pulse P4 by apredetermined time period of less than 500-2000 microseconds andpreferably less than 50-500 microseconds. A weighted average time is theintegral of a pulse over the pulse interval divided by the pulseamplitude of the pulse interval. The rise time and fall time of a pulsecan affect the weighted average time of the pulse.

Similarly, the peak PK3 of pulse P3 is displaced from the peak PK4 ofpulse P4 by a predetermined time period of less than 500-2000microseconds and preferably less than 50-500 microseconds. The rise timeof a pulse can affect the peak time of the pulse. Objectives of theinvention also can be achieved using combinations of the foregoingtiming relationships. For example, the time delay between the firstpulse and the second pulse can be the time difference between a firstweighted average time of the first pulse and a second weighted averagetime of the second pulse. Alternatively, the time delay can be the timedifference between a first peak time of the first pulse and a secondpeak time of the second pulse.

Referring to FIGS. 3 and 8, line L1 represents the edge of athree-dimensional locus L1A of cells in excitable tissue in which pulseP1 applied to electrode 18A results in a transmembrane potential whichcan be represented by curve TPA1 of FIG. 8. That transmembrane potentialis less than the transmembrane potential threshold TPT for cells ofinterest in that locus. That transmembrane potential is comprised of aconstant resting potential and a depolarization caused by application ofpulse P1 to electrode 18A. Thus, locus L1A, which results from pulse P1being applied to electrode 18A without a recent pulse being applied toelectrode 16A is an area having subthreshold potential since TPA1 isless than the transmembrane potential threshold TPT.

Similarly, referring to FIGS. 4 and 8, line L2 represents the edge ofanother three-dimensional locus L2A in which the application of pulse P2to electrode 16A results in a transmembrane potential which also can berepresented by the transmembrane potential curve TPA2 of FIG. 8. Thattransmembrane potential is less than the transmembrane potentialthreshold TPT for cells of interest in that locus. That transmembranepotential is the sum of a constant resting potential and adepolarization potential caused by application of pulse P2 to electrode16A. Thus, locus L2A, which results from pulse P2 being applied toelectrode 16A without a recent pulse being applied to electrode 18A isalso an area of subthreshold potential since TPA2 is less than thetransmembrane potential threshold TPT.

FIG. 5 illustrates a locus L3A representing the intersection of loci L1Aand L2A in which the combined potentials induced in locus L3A frompulses P1 and P2 create an action potential in cells of interest inlocus L3A as illustrated by the transmembrane potential TPB in FIG. 8.The total potential in cells in locus L1A outside locus L3A isillustrated by the transmembrane potential TPA1 in FIG. 8. Since TPA iis lower than the transmembrane potential threshold TPT, the totalpotential is a subthreshold potential, and there is no action potentialcreated in cells in locus L1A outside L3A. The total potential createdin cells in locus in L2A outside L3A is illustrated by transmembranepotential TPA2 in FIG. 8. Again, the total potential is a subthresholdpotential, and there is no action potential created in cells in locusL2A outside locus L3A.

The suprathreshold potential induced in cells in locus L3A results froma superposition of the subthreshold potentials TPA1 and TPA2 created inthat area by excitation from a pulse applied to electrode 16A and fromanother pulse applied to electrode 18A. Locus L3A has nerve cells thatget action potentials resulting from this suprathreshold potentialinduced in that locus. The total potential in cells in locus L3A isillustrated by the transmembrane potential TPB of FIG. 8. Thattransmembrane potential is comprised of the constant resting potentialand the superposition of depolarizations from application of pulse P1 toelectrode 18A and pulse P2 to electrode 16A.

Referring to FIGS. 6 and 8, line L4 represents the edge of anotherthree-dimensional locus L4A having subthreshold potential resulting fromthe application of a pulse P1 to electrode 18A having an amplitudegreater than amplitude A1. Line L5 represents the edge of anotherthree-dimensional locus L5A having subthreshold potential resulting fromthe application of a pulse P2 to electrode 16A having an amplitude lessthan amplitude A2. The intersection of loci L4A and L5A creates a locusL6A in which a suprathreshold action potential results from asuperposition of subthreshold potentials created by application ofpulses P1 and P2. Locus L6A is moved mostly to the right relative tolocus L3A shown in FIG. 5. Action potentials are not induced outsidelocus L6A since the area outside that locus has subthreshold potentials.

Referring to FIGS. 7 and 8, line L8 represents the edge of anotherthree-dimensional locus L8A having subthreshold potential resulting fromthe application of a pulse P2 to electrode 16A having an amplitudegreater than amplitude A2. Line L7 represents the edge of anotherthree-dimensional locus L7A having subthreshold potential resulting fromthe application of a pulse P1 to electrode 18A having an amplitude lessthan amplitude A1. The intersection of loci L7A and L8A creates a locusL9A in which a suprathreshold action potential is induced from asuperposition of subthreshold potentials created by application of bothpulses P1 and P2. It will be noted that the locus L9A is moved to theleft compared with locus L3A shown in FIG. 5. Action potentials are notinduced outside locus L9A since the area outside that locus hassubthreshold potentials.

A benefit of utilizing the neurophysiological principle of“electrotonus” is that the area of suprathreshold potential can becontrolled by varying the time delay between application of the twopulses to each respective driven electrode for creating the areas ofsubthreshold potential. Referring to FIG. 8, this time delay can be thetime period between the end of pulse P1 at time T2 and the start ofpulse P2 at time T3.

Principles of “electrotonus” indicate that a potential for any nervecell decays with a RC time IQR constant after a stimulation pulse hasbeen applied to that nerve cell. R is a resistive value determined bythe resistive characteristic for that nerve cell, and C is a capacitivevalue determined by the capacitive characteristic for that nerve cell.

Because of this memory effect of electrotonus, the transmembranepotential created within a nerve cell by a pulse starts to decay at theend of the excitation pulse, and this transmembrane potential is afunction of time. By taking advantage of this time variation of thetransmembrane potential, the area of suprathreshold potential can beadjusted by correspondingly varying the time delay between the pulsesthat are applied to two electrodes that each produce a subthresholdarea.

This benefit is further illustrated in FIGS. 12-15 where elementssimilar to elements in the prior figures are labeled with the samenumeric label. FIG. 12 illustrates the case where the pulses applied tothe two cathodes follow closely in time. Element 12 is a simplifiedillustration of electrically excitable tissue such as spinal cordtissue. Pulse P2 immediately follows after the end of pulse P1, and thetime delay between the end of pulse P1 at T2 and the start of pulse P2at T3 is small in this case.

Line L10 represents the isopotential line defining a subthreshold areaL10A created by application of pulse P1 at electrode 18A. Line L11represents the isopotential line defining another subthreshold area L11Acreated by application of pulse P2 at electrode 16A. (A return electrodeis not shown in FIGS. 12-15 since that electrode is typically located ona different plane from the shown tissue plane 12 or on a more remotelocation on the body carrying the tissue 12 such as at the metallic caseof the pulse generator 14 of FIG. 1.) Each isopotential line varies withtime and progresses away from the electrode producing that isopotentialline during the application of a pulse to that electrode and recedesback toward that electrode after the completion of the pulse by theprinciple of “electrotonus”. In FIG. 12, the isopotential lines L10 andL11 are what result at the end of pulse P2 at time T4. These individualsubthreshold areas by themselves do not have sufficient potentialchanges to induce an action potential within tissue 12. However, asuperposition of the subthreshold potential areas at time T4 creates anarea L12A of suprathreshold potential that is greater than thetransmembrane potential threshold such that nerve cells within that areahave an action potential induced therein.

FIG. 13 shows a case where the two pulses P1 and P2 are more separatedin time than the case illustrated in FIG. 12. The transmembranepotentials in FIG. 13 that are created in electrically excitable tissue12 are those that remain at the end of pulse P2 at time T4. By thattime, the application of pulse P1 was already completed at time T2.Isopotential line L13 defines the subthreshold area L13A that remainsfrom the application of pulse P1 to electrode 18A by time T4.Isopotential line L14 defines the subthreshold area L14A that is createdby application of pulse P2 to electrode 16A by time T4.

These individual subthreshold areas by themselves do not have sufficientpotential changes to induce an action potential. However, asuperposition of the subthreshold potential areas creates an area L15Aof suprathreshold potential that is greater than the transmembranepotential threshold such that nerve cells within that area have anaction potential induced therein. Note that the area of suprathresholdpotential L15A of FIG. 13 differs from the area of suprathresholdpotential L12A of FIG. 12 because of the larger time delay between theend of pulse P1 at T2 and the start of pulse P2 at T3 in FIG. 13 than inFIG. 12.

Similarly, FIG. 14 shows a case where the two pulses P1 and P2 are stilleven more separated in time than those of FIG. 13. FIG. 14 shows theisopotential lines that are created by pulses P1 and P2. at the end ofpulse P2 at time T4. The isopotential line L16 defines the subthresholdarea L16A created by the application of pulse P1 at electrode 18A bytime T4, and the isopotential line L17 defines the subthreshold areaL17A created by the application of pulse P2 at electrode 16A by time T4.

The individual subthreshold areas within isopotential lines L16 and L17by themselves do not have sufficient potential changes to induce anaction potential. However, a superposition of subthreshold potentialareas creates an area L18A of suprathreshold potential that is greaterthan the transmembrane potential threshold such that nerve cells withinthat area have an action potential induced therein. Note that because ofthe larger delay between pulses P1 and P2, isopotential line L16 hasreceded further toward electrode 18A by the end of pulse P2 at time T4,and the area L18A of suprathreshold potential has decreased and hasshifted more toward electrode 18A.

Finally, FIG. 15 shows a case where pulse P1 and P2 have a time delaysufficiently far enough such that no area of suprathreshold potential iscreated within the electrically excitable tissue 12. Isopotential lineL19 is the result of application of pulse P1 at electrode 18A by the endof pulse P2 at time T4, and isopotential line L20 is the result ofapplication of pulse P2 at electrode 16A by time T4. Because of thelarge delay between pulses P1 and P2, isopotential line L19 has recededso far back toward electrode 18A that there is no area of superpositionof the two subthreshold areas created by isopotential lines L19 and L20within tissue 12.

The ability to move the locus in which action potentials are induced bycontrolling the area of superposition of subthreshold potential areas isan important feature. In many therapies, it is important to preventaction potentials being induced in gray matter 34 or dorsal horns 36 and37, dorsal roots 38 and 40, dorsal lateral columns 47 or peripheralnerves 42 and 44 in order to minimize the possibility of causing pain,motor effects, or uncomfortable paresthesia. With the describedtechniques, the locus in which action potentials are induced (e.g., L3A,L6A, L9A, L12A, L15A, or L18A) can be manipulated to a desired area ofthe dorsal columns 46 without inducing action potentials in dorsal horns36 and 37, gray matter 34 or dorsal lateral columns 47 or dorsal rootganglia 38 and 40. Moreover, the ability to move the locus in whichaction potentials are induced drastically reduces the accuracy necessaryfor surgically implanting electrodes 16A and 18A, and may eliminate theneed for surgical lead revisions.

Another advantageous result from being able to determine the locus ofexcitation by controlling the area of suprathreshold potential fromsuperposition of subthreshold potential areas is that the location ofthe two driven electrodes 16A and 18A and the return electrode withrespect to each other is not critical to the practice of this invention.In contrast to the invention disclosed by Holsheimer et al. in U. S.Pat. No. 5,501,703, the two driven electrodes and the return electrodein the present invention are not optimally spaced in line with respectto each other. In fact, the return electrode of the present inventioncan be located remotely from the driven electrodes 16A and 18A near apoint up or down the spinal column or another part of the body carryingthe spine being excited. Alternatively, there may be more than onereturn electrode within the body.

FIG. 11 illustrates a preferred timing relationship between pulse P7applied to electrode 18A and pulse P8 applied to electrode l6A.Currently available pulse generators use a biphasic pulse to insure nonet direct current flows into the tissue. This is known ascharge-balanced pulsing, and is accomplished by driving the pulsenegative for a duration of time. For example, in FIG. 11, pulse P8 has anet charge delivered proportional to A2*(T4-T3). This injected charge isbalanced by the negative pulse P10, whose charge is proportional toA3*(T5-T4), where A3<<A2 and (T5-T4)>>(T4-T3). Similar principles applyeven if the first and second pulses are not of constant amplitude.

In a preferred embodiment, pulse P7 may be generated with a trailingnegative pulse P9 from time T4 to time T5, so that the output onelectrode 18A is substantially at neutral or 0 potential until thetermination of pulse P8 at time T4. Having this delay in chargebalancing prevents the loss of potential in adjacent tissue thatotherwise would occur if pulse P9 immediately followed pulse P7 andoverlapped with pulse P8, thus offsetting the benefit of pulse P8. Attime T4 both negative pulses P9 and P10 begin in order to maintain thecharge balance in tissue adjacent to the respective electrodes 18A and16A.

In another embodiment of the present invention, the present inventionutilizes an array of electrodes to more finely control the shape of thefield of excitation. These electrodes provide multi-channel stimulationof the desired treatment area. Multi-channel stimulation generallyrefers to the stimulation of several sites at differing pulse parametersincluding, for example and without limitation, pulse amplitude, pulsewidth, pulse frequency, pulse shape, pulse rise, pulse fall, pulse peak,and pulse polarity. These pulses may be either. voltage or currentpulses. For example, if one site receives a voltage or current pulse,and then another site gets a pulse at the same time, an. overlappingtime, or a separate time. The stimulation and steering techniquesdiscussed above may be used to achieve suprathreshold potentials withinthe desired treatment areas. The field of excitation may be created andcontrolled using any number of techniques, including but not limited to,simultaneous pulses of two cathodal amplitudes and one anode, paired(delayed) pulses using two or more electrodes, a combination ofsimultaneous and paired (delayed) pulses among various electrodes, andconventional full polarity pulses of anodes and cathodes. Each of thesetechniques are discussed herein in further detail.

FIG. 16 shows a way to perform two-dimensional steering using an array1600 of electrodes. These electrodes may be placed on a paddle lead ormay be positioned across three adjacent percutaneous leads. Array 1600may include a central cathode C1 and up to four surrounding anodesC2-C5. Simultaneous anodal pulses can then be delivered, each with theirown potential, to the surrounding electrodes C2-C5S. Advantageously,the. electric field may be steered in any number of directions over a2-dimensional space. As exemplified in FIG. 17, the effect may besteered from left to right by using electrodes C1, C2 and C4 and turningoff electrodes C3 and C5. Further, as exemplified in FIG. 18, the effectmay be steered from top to bottom by using electrodes C1, C3 and C5.FIG. 19 illustrates a method to shield activation of cells in a lowerdirection and to maintain the field of excitation in the middle andslightly upward. The field of excitation L19 is skewed by using onlyanodal electrodes C2-C4, where electrode C3 is stronger in voltage thanelectrodes C2 and C4. FIG. 20 illustrates steering of field L20 along adiagonal by using surrounding electrodes C2-C5 but with varyingvoltages.

As shown in FIG. 21, central electrode C1 may also be eliminatedaltogether. In this case, one of the remaining electrodes, say C2 is themost cathodal (−), and the remaining three electrodes C2-C4 can beprogrammed to have three equal or different anodal voltages to providethe necessary steering of the field L21. Although the currents fromelectrode C2 move off in the other direction in a less controlledmanner, this embodiment advantageously avoids current waste that wouldbe present with a nearby central cathode C1.

FIGS. 22(a-e) shows a number of electrode shape configurations that mayprevent unnecessary shorting of currents in the epidural space, or helpdirect energy into certain patterns. FIG. 22(a) has greater efficiencysince the electrodes are relatively far from each other. FIGS. 22(b andc) depict electrodes having relatively larger surface areas, therebyreducing resistance and allowing for higher currents. FIG. 22(d) hasfour electrodes farther apart forming a ring. FIG. 22(e) depictsrelatively smaller electrodes that are further apart from each other toincrease efficiency and minimize shunting of current between theelectrodes.

FIG. 23 illustrates a similar concept but with 6 electrodes in a ringpattern to provide greater control of the direction of the electricfield. Here, up to five or more anodal voltage levels may be used (ifone is most cathodal), or up to six cathodal voltage levels may be used(if there is one distant anode, say, on a power source case). Thoseskilled in the art will appreciate that even other electrodeconfigurations can be used together with more simultaneous pulses orvarying amplitudes. Delivery of subthreshold pulses at various times mayresult in a two-dimensional locus of superactivation.

FIG. 24 shows the initial cross-pattern of five electrodes C1-CS withsome outer electrodes C6-C9. If any of the ring of electrodes C2-C5 ismade a cathode, electrode C1 may be turned off and one or more outerelectrodes C6-C9 can be made anodal to help maintain the field ofexcitation bounded on that side. FIG. 25 is yet another embodimenthaving five or more electrodes in an outer ring that could be anodal tocontain the electric field toward the center.

Advantageously, these 2-dimensional configurations may be used to createsuprathreshold potential areas as discussed above. Stimulation may beprovided using a two-dimensional array of electrodes and configuring arange of anode/cathode relationships from the array. Moreover,simultaneous pulsing may be achieved by applying pulses of varyingamplitudes to a selected group of cathodes in the array.

The advantages of the invention described herein can be generalized toapplications for exciting any electrically excitable tissue within anyorganism, in addition to such tissue within a spine. Particularly, thesame techniques of the present invention could be used for intraspinal,cortical, deep brain, peripheral nerve, heart or other muscle or organstimulation as well. Further, the fields to be generated might haveeither constant current or constant voltage sources. Moreover, theinvention can be generalized to using more than two cathodal electrodesto generate more than two subthreshold areas to be superposed ingenerating the suprathreshold potential area. Accordingly, the forgoingdescription is by way of example only and is not intended to belimiting. The invention is limited only as defined in the followingclaims and equivalents thereof.

We claim:
 1. An apparatus for inducing action potentials at anadjustable locus of electrically excitable tissue of an organism,comprising in combination: (A) a plurality of electrodes forming a2-dimensional array and adapted to be implanted adjacent to the tissue;(B) at least one return electrode capable of being disposed within theorganism; (C) a first set of at least one electrode within the pluralityof electrodes capable of being driven with a first pulse having a firstpulse parameter to generate a first subthreshold potential area in thetissue with respect to the return electrode; (D) a second set of atleast one electrode within the plurality of electrodes capable of beingdriven with a second pulse having a second pulse parameter to generate asecond subthreshold potential area in the tissue with respect to thereturn electrode; and E) a generator capable of providing the firstpulse with the first pulse parameter being adjustable to cause a firstcorresponding adjustment in the first subthreshold area and providingthe second pulse with the second pulse parameter being adjustable tocause a second corresponding adjustment in the second subthreshold area,wherein a superposition of the first subthreshold area and the secondsubthreshold area results in a suprathreshold potential area of theadjustable locus where the action potentials are induced.
 2. Theapparatus of claim 1, wherein the first and second pulse parameters areselected from the group consisting of pulse width, pulse amplitude,pulse frequency, pulse rise time, pulse fall time, and pulse shape. 3.The apparatus of claim 1, wherein an increase of a first pulse widthresults in an increase of the first subthreshold area and in an increaseof the suprathreshold area toward the second set of electrodes.
 4. Theapparatus of claim 1, wherein an increase in a first pulse width and adecrease in a second pulse width results in a shift of thesuprathreshold area toward the second set of electrodes.
 5. Theapparatus of claim 1, wherein the first pulse has a first begin time anda first end time and the second pulse has a second begin time and asecond end time, and wherein the generator is further capable ofadjusting a time delay between the first end time of the first pulse andthe second begin time of the second pulse, wherein the time delaydetermines a size and location of the suprathreshold potential area. 6.The apparatus of claim 5, wherein the generator is further capable ofincreasing the time delay to thereby cause a decrease in the size ofsaid suprathreshold potential area and a shift of the suprathresholdpotential area toward the first set of electrodes.
 7. The apparatus ofclaim 1, wherein the first pulse has a first weighted average time andthe second pulse has a second weighted average time, wherein thegenerator is further capable of adjusting a time delay between the firstand second weighted average times, wherein the time delay determines asize and location of the suprathreshold potential area.
 8. The apparatusof claim 7, wherein the generator is further capable of increasing thetime delay to thereby cause a decrease in the size of saidsuprathreshold potential area and a shift of the suprathresholdpotential area toward the first set of electrodes.
 9. The apparatus ofclaim 1, wherein the first pulse has a first peak time and the secondpulse has a second peak time, wherein the generator is further capableof adjusting a time delay between the first and second peak times,wherein the time delay determines a size and location of thesuprathreshold potential area.
 10. The apparatus of claim 9, wherein thegenerator is further capable of increasing the time delay to therebycause a decrease in the size of the suprathreshold potential area and ashift of the suprathreshold potential area toward the first set ofelectrodes.
 11. The apparatus of claim 1, wherein the first and secondsets of electrodes are cathodes and the return electrode is an anode,and wherein the return electrode is capable of being placed away fromthe first and second sets of electrodes such that potential on thereturn electrode does not perturb the first and second subthresholdpotential areas.
 12. The apparatus of claim 11, wherein the returnelectrode is part of a metallic case holding the generator.
 13. Theapparatus of claim 1, wherein the first and second pulses aresimultaneous in time.
 14. A method for inducing action potentials at anadjustable locus of electrically excitable tissue within an organismcomprising the steps of: (A) delivering a first pulse of electricalstimulation adjacent to the tissue using a first set of at least onecathode within a 2-dimensional array of electrodes implanted near thetissue to generate a first subthreshold potential area in the tissuewith respect to a return electrode disposed within the organism; (B)delivering a second pulse of electrical stimulation adjacent to thetissue using second set of at least one cathode within the 2-dimensionalarray to generate a second subthreshold potential area in the tissuewith respect to the return electrode; (C) adjusting a first pulseparameter of the first pulse to cause a corresponding adjustment of thefirst subthreshold potential area; and (D) adjusting a second pulseparameter of a second pulse to cause a corresponding adjustment of thesecond subthreshold potential area, wherein a suprathreshold potentialarea of the adjustable locus of the tissue where the action potentialsare induced results from a superposition of the first and secondsubthreshold potential areas.
 15. The method of claim 14, wherein thestep of adjusting the first pulse parameter further includes the step ofincreasing a first pulse width to cause an increase of the firstsubthreshold area and an increase of the suprathreshold area toward thesecond set of cathodes.
 16. The method of claim 14, wherein the step ofadjusting the first pulse parameter further includes the step ofdecreasing a first pulse width to cause a decrease of the firstsubthreshold area and a decrease of the suprathreshold area toward thesecond set of cathodes.
 17. The method of claim 14, wherein the step ofadjusting the first pulse parameter further includes the step ofincreasing a first pulse width and the step of adjusting the secondpulse parameter includes the step of decreasing a second pulse width tocause a shift of the suprathreshold area toward the second set ofcathodes.
 18. The method of claim 14, wherein the first pulse has afirst begin time and a first end time and the second pulse has a secondbegin time and a second end time, and wherein the method furtherincludes the step of adjusting a time delay between the first end timeof the first pulse and the second begin time of the second pulse,wherein the time delay determines a size and location of thesuprathreshold potential area.
 19. The method of claim 14, wherein thefirst pulse has a first weighted average time and the second pulse has asecond weighted average time, and wherein the method further includesthe step of adjusting a time delay between the first and second weightedaverage times, wherein the time delay determines a size and location ofthe suprathreshold potential area.
 20. The method of claim 14, whereinthe first pulse has a first peak time and the second pulse has a secondpeak time, and wherein the method further includes the step of adjustinga time delay between the first and second peak times, wherein the timedelay determines a size and location of the suprathreshold potentialarea.
 21. The method of claim 14, further including the step of placingthe return electrode away from the adjustable locus of the tissuewherein the action potentials are induced such that potential on thereturn electrode does not perturb the first and second subthresholdpotential areas.
 22. The method of claim 14, wherein the steps ofdelivering are performed so that the first and second pulses aresimultaneous in time.
 23. An apparatus for inducing action potentials atan adjustable locus of electrically excitable tissue of an organism,comprising in combination: (A) at least one return electrode capable ofbeing disposed within the organism; (B) a plurality of electrodesforming a 2-dimensional array and adapted to be implanted adjacent tothe tissue, wherein at least two electrodes within the plurality ofelectrodes are each capable of being independently driven, wherein eachof the at least two electrodes is capable of delivering a correspondingpulse having a corresponding pulse parameter to generate a correspondingsubthreshold potential area in the tissue with respect to the returnelectrode; and (C) a generator capable of providing the correspondingpulses independently to the at least two electrodes with thecorresponding pulse parameters being adjustable to cause correspondingadjustments in the corresponding subthreshold areas, wherein asuperposition of at least two corresponding subthreshold areas resultsin a suprathreshold potential area of the adjustable locus where theaction potentials are induced.
 24. The apparatus of claim 23, whereinthe corresponding pulse parameter is selected from the group consistingof pulse width, pulse amplitude, pulse frequency, pulse rise time, pulsefall time, and pulse shape.
 25. The apparatus of claim 23, wherein eachcorresponding pulse has a begin time and an end time, and wherein thegenerator is further capable of adjusting a time delay between the endtime of one of the corresponding pulses and the begin time of anotherone of the corresponding pulses, wherein the time delay determines asize and location of the suprathreshold potential area.
 26. Theapparatus of claim 25, wherein an increase in the time delay results ina decrease in the size of said suprathreshold potential area.
 27. Theapparatus of claim 23, wherein each corresponding pulse has a weightedaverage time, and wherein the generator is further capable of adjustinga time delay between the weighted average time of one of thecorresponding pulses and the weighted average time of another one of thecorresponding pulses, wherein the time delay determines a size andlocation of the suprathreshold potential area.
 28. The apparatus ofclaim 27, wherein an increase in the time delay results in a decrease inthe size of said suprathreshold potential area.
 29. The apparatus ofclaim 23, wherein each corresponding pulse has a peak time, and whereinthe generator is further capable of adjusting a time delay between thefirst peak time of one of the corresponding pulses and the first peaktime of another one of the corresponding pulses, wherein the time delaydetermines a size and location of the suprathreshold potential area. 30.The apparatus of claim 29, wherein an increase in the time delay resultsin a decrease in the size of the suprathreshold potential area.
 31. Theapparatus of claim 23, wherein generator is capable of causing the atleast two electrodes to be cathodes and the return electrode to be ananode, and wherein the return electrode is capable of being placed awayfrom the at least two electrodes such that potential on the returnelectrode does not perturb the corresponding subthreshold potentialareas.
 32. The apparatus of claim 31, wherein the return electrode ispart of a metallic case holding the generator.
 33. The apparatus ofclaim 23, wherein at least two of the corresponding pulses aresimultaneous in time.
 34. A method for inducing action potentials at anadjustable locus of electrically excitable tissue within an organismusing a 2-dimensional array of electrodes comprising the steps of: (A)implanting the electrodes near the tissue; (B) selecting at least two ofthe electrodes; (C) for each of the selected electrodes, delivering acorresponding pulse of electrical stimulation adjacent to the tissue togenerate a corresponding subthreshold potential area in the tissue withrespect to a return electrode disposed within the organism, thecorresponding pulse having a corresponding pulse parameter; and (D)adjusting the corresponding pulse parameter for at least one of theselected electrodes to cause an adjustment of the correspondingsubthreshold potential area, wherein a suprathreshold potential arearesults from a superposition of the corresponding subthreshold potentialareas.
 35. The method of claim 34, wherein the step of adjusting thefurther includes the step of increasing a pulse width to cause anincrease of the corresponding subthreshold area.
 36. The method of claim34, wherein the step of adjusting further includes the step ofdecreasing a pulse width to cause a decrease of the correspondingsubthreshold area.
 37. The method of claim 34, wherein each of thecorresponding pulses has a begin time and an end time, and wherein themethod further includes the step of adjusting a time delay between theend time of one of the corresponding pulses and the begin time anotherone of the corresponding pulses, wherein the time delay determines asize and location of the suprathreshold potential area.
 38. The methodof claim 34, wherein each of the corresponding pulses has a weightedaverage time, and wherein the method further includes the step ofadjusting a time delay between the weighted average time of one of thecorresponding pulses and the weighted average time of another one of thecorresponding pulses, wherein the time delay determines a size andlocation of the suprathreshold potential area.
 39. The method of claim34, wherein each of the corresponding pulses has a peak time, andwherein the method further includes the step of adjusting a time delaybetween the peak time of the one of the corresponding pulses and thepeak time of another one of the corresponding pulses, wherein the timedelay determines a size and location of the suprathreshold potentialarea.
 40. The method of claim 34, further including the step of placingthe return electrode away from the adjustable locus of the tissuewherein the action potentials are induced such that potential on thereturn electrode does not perturb the corresponding subthresholdpotential areas.
 41. The method of claim 34, wherein the steps ofdelivering are performed so that at least two of the correspondingpulses are simultaneous in time.